This application addresses major issues in aging research: identification of risk factors for disease and death, prevention of decline in cognitive and physical functioning, and in end-of-life planning. These issues will be addressed in the Precursors Study, a prospective, longitudinal study of 1,337 former Johns Hopkins medical students followed from an average age of 22 to 71 years. This study has yielded insights into aging that complement cross-sectional or short-term prospective studies of larger populations. The cohort has high levels of education, socioeconomic status, and access to health care. This homogeneity controls for these potent modifiers of health and functional outcomes and permits a relatively unconfounded and precise estimate of the risk associated with other exposures. As we begin our 55th year of follow up, we will continue our detailed description of aging and the onset of disease. We will determine the risk of CVD and other diseases associated with characteristics assessed repeatedly throughout the life course. We expect that relative risk of CVD will decrease at older age of assessment and will use the richness of the information available to dissect out the reasons for this age-related decrement. In addition, we will determine associations of characteristics from youth to old age with level of and short-term change in cognitive function, as well as interaction with the e4 allele of Apolipoprotein E. Most studies of risk factors for cognitive decline are cross-sectional in nature or have follow-up times within the 'incubation period' of dementia, design features that impede accurate data collection because of memory impairment. We will also repeatedly assess physical functioning to determine risk factors for greater rate of decline associated with aging. Lastly, we will describe change in preferences for end-of-life treatment and how it is influenced by incident disease, life events, and mental health as well as personal characteristics assessed prospectively over the 50 plus years of follow-up. The Precursors Study provides a unique opportunity to test whether potentially modifiable factors, assessed prospectively up to 50 years before, relate to mental health and physical functioning in late life, when these factors might act, and for whom.